SSRIs (Selective Serotonin Reuptake Inhibitors)

Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed category of antidepressants. These medications have a strong reputation for both safety and effectiveness. Developed in the past 20 years, SSRIs are typically the first choice for physicians when treatment requires the prescription of antidepressants. Unlike many tricyclic antidepressants, SSRIs have less affinity for α-adrenergic, histamine, and cholinergic receptors and thus produce fewer adverse effects than most other classes of antidepressants.

History of SSRIs

According to studies, as many as one in 10 Americans are taking some type of antidepressant and for women in their 40s and 50s, that number is one in four. Treatment for depression using psychotropic medication began in the 1950s with monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). These drugs, while helpful to many experiencing depression, also came with a wide range of harmful side effects because of their broad targeting of biological systems. This limited their ability to be prescribed and used in research, which prompted drug manufacturers to begin working on a depression treatment that only targeted the serotonin system in an attempt to affect a person’s well-being and happiness without causing a host of other effects.

In the late 1970s, neuroscientists developed a selective serotonin reuptake inhibitor drug called zimelidine that was based on an antihistamine drug. It was brought to the market in 1982 and sold under the brand names Zimeldine, Normud, and Zelmid. Rare reports emerged that claimed the drug caused Guillain–Barré syndrome, a polyneuropathy disorder that affects the peripheral nervous system, which later caused it to be withdrawn from the market. As a result, a newer class of SSRI drugs came into development, and scientists produced two new types of this drug: fluvoxamine and fluoxetine. Fluvoxamine became the first drug to be approved by the FDA to treat obsessive compulsion, and fluoxetine was approved by the FDA in 1987 to treat major depression.

Fluoxetine, usually marketed under the brand name Prozac, was followed by the introduction of Zoloft in 1991 and Paxil in 1992. Fluoxetine is now one of the most prescribed antidepressants across the globe. The discovery of fluoxetine was the result of a search for compounds that could have an affinity for monoamine receptors. The goal of this search was to find specific compounds that did not affect cholinergic, adrenergic, or histamine receptors. It was first hailed as a miracle drug used to treat depression and by 1990 was the most prescribed antidepressant in the world, earning drug manufacturers more than $1 billion per year by itself. It is prescribed to people ranging in age from pre-teen to retiree and is even used in veterinary medicine.

Fluoxetine was one of the first drugs to be mass-marketed to consumers, and while it has opened many new doors for the treatment of depression, it has also led to the pathologization of depression and reduced its treatment to pills alone for many. Many in the health care community believe the drug is over-prescribed and sometimes ineffectively prescribed, when it does not accompany any other type of treatment such as psychotherapy.

How Do SSRIs Work?

SSRIs act on the serotonin transporter (SERT or 5-HTT), which is responsible for taking up serotonin from a synaptic cleft back to the presynaptic neuron. These transporters are glycoproteins present in synapses. Their function is to take up extra quantities of neurotransmitters from these synapses and transfer them back to presynaptic nerves for further use.

Serotonin—or 5-HT—has primary functions that include mood regulation. For most people, boosting serotonin results in improved mood and can have beneficial effects for those experiencing depression or anxiety. SSRIs are called "selective" because they have relatively little or no effect on other neurotransmitters present in the body.

Most prescriptions for these medications consist of a once-daily or even a once-weekly dosage. Because the amount of serotonin in the brain increases very slowly, these medications usually require up to four weeks to reach their full strength. It is even possible that a person will feel worse during the first week or two of treatment. As such, people taking any SSRI medication should report any unusual symptoms to their doctor.

It should also be noted that nearly all antidepressant medications work better when paired with some type of psychotherapy. Medications can help manage the overt symptoms of depression, but they do not address the root causes or negative feelings, and they also do not help a person develop positive coping strategies should they experience symptoms of depression, anxiety, or panic in the future. If you are prescribed an SSRI or any other prescription antidepressant, please consider finding a qualified therapist you trust to help you better understand your mental health condition.

Side Effects

It is possible to experience unwanted side effects while taking SSRI medications. You should discuss your health history with your doctor before beginning any new medication and notify your doctor if you experience changes in your health while taking an SSRI. Possible side effects from these medications can include:

Cardiovascular effects: Hypertension and increased heart rate may occur when taking SSRIs, although this side effect is very rare. Hypotension may occur as well. Orthostatic hypotension—the medical term for the dizzy feeling you get when standing up or stretching too quickly—and fainting have also been reported. Palpitations, flushes, and arrhythmias are also possible adverse drug reactions.

Gastrointestinal effects: Constipation, dry mouth, anorexia, weight gain or loss, and nausea are some common adverse effects of SSRIs.

Nervous system effects: Most common effects include dizziness, headache (unrelated to blood pressure), drowsiness, sleep disturbances (insomnia, hypersomnia), confusion, and memory loss. At high doses, worsening of anxiety, depression, and suicidal ideation have been noticed. Seizures have been reported as well.

Hepatic effects: Liver damage is likely when a patient is already suffering from chronic liver disease. However, the risk is very low for people using SSRIs. Reduction of the dose is recommended, but a pharmacist or physician should be consulted before reaching this decision.

Adverse effects on the urinary and reproductive systems: Impotence, delayed and premature ejaculation, and anorgasmia have been reported. Hyponatremia (abnormally low sodium) is a major adverse effect of SSRIs and SNRIs.

Abnormal bleeding: Abnormal bleeding must be reported. SSRIs should be used with caution if a person is taking anticoagulants, such as warfarin and aspirin.

Pregnancy and SSRIs: There is not enough data about these medications and pregnancy to make a definitive recommendation. However, in animals, this category of drugs has demonstrated some teratogenic effects. Fluoxetine, for example, when given to pregnant mice prolonged the gestation period. SSRI use is considered an option for pregnant and nursing mothers, but a physician must balance the benefit to risk ratio before prescribing them.

Other side effects: Visual disturbances, mydriasis, thrombocytopenia, anemia, alopecia, arthralgia, and lupus-like syndrome are reported by some people using SSRI drugs.

Withdrawal

A washout period of at least 15 to 20 days is required after the discontinuation of treatment with SSRI drugs. Officially, SSRIs are not addictive, which is why they are usually prescribed over benzodiazepines to treat depression, although that classification has come under fire in recent years. Nevertheless, suddenly discontinuing an SSRI medication may lead to unpleasant withdrawal-like symptoms. These may include nausea, headache, lethargy, insomnia, fatigue, depression, anxiety, mania, and even flu-like symptoms. It is recommended to reduce doses at equal intervals so that withdrawal symptoms can be avoided.

References:

Fitzpatrick, L. (2010, January 7). A Brief History of Antidepressants. Time. Retrieved March 6, 2015, from http://content.time.com/time/health/article/0,8599,1952143,00.html.

Rabin, R. (2013, August 12). A Glut of Antidepressants. The New York Times. Retrieved March 6, 2015, from http://well.blogs.nytimes.com/2013/08/12/a-glut-of-antidepressants/?_r=0.

Smith, M., & Segal, J. (2015, February 1). Types of Antidepressants and Their Side Effects. Retrieved from http://www.helpguide.org/articles/depression/types-of-antidepressants-and-their-side-effects.htm.

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